This project aims to understand the mechanisms which underlie the changes in renal reabsorption and metabolism of ketoacids in starvation and experimental diabetic ketoacidosis in the rat. First through in vivo studies the simultaneous rates of renal reabsorption and utilization of ketoacids will be quantitated at progressively higher blood [ketoacid]. The relationships between filtered loads and reabsorption rates and renal utilization rates of ketoacids will thus be evaluated. The nature of the changes in renal transport of ketoacids will be then explored using isolated membrane vesicles of rat proximal tubular cells. Kinetic studies of ketoacid transport in brush border and basolateral membrane vesicles are contemplated. The nature of the metabolic changes observed will be explored in isolated proximal tubules of rat kidney and in isolated renal cortical mitochondria.